Neurofarba Department, Sezione di Chimica Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Firenze, Italy.
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):758-763. doi: 10.1080/14756366.2021.1897802.
We report the first activation study of the β-class carbonic anhydrase (CA, EC 4.2.1.1) encoded in the genome of the protozoan pathogen , TvaCA1. Among 24 amino acid and amine activators investigated, derivatives incorporating a second carboxylic moiety, such as L-Asp, L- and D-Glu, were devoid of activating effects up to concentrations of 50 µM within the assay system, whereas the corresponding compounds with a CONH moiety, i.e. L-Gln and L-Asn showed modest activating effects, with activation constants in the range of 26.9 - 32.5 µM. Moderate activation was observed with L- and D-DOPA, histamine, dopamine, serotonin, (2-Aminoethyl)pyridine/piperazine and morpholine (K's ranging between 8.3 and 14.5 µM), while the best activators were L-and D-Trp, L-and D-Tyr and 4-amino-Phe, which showed K's ranging between 3.0 and 5.1 µM. Understanding in detail the activation mechanism of β-CAs may be relevant for the design of enzyme activity modulators with potential clinical significance.
我们报告了首例原核生物病原体 中编码的β 类碳酸酐酶（CA，EC 4.2.1.1）的激活研究。在研究的 24 种氨基酸和胺类激活剂中，在测定系统中，含有第二个羧酸基的类似物，如 L-天冬氨酸、L-和 D-谷氨酸，其浓度高达 50µM 时也没有激活作用，而含有 CONH 基的相应化合物，即 L-谷氨酰胺和 L-天冬酰胺，表现出适度的激活作用，其激活常数在 26.9µM-32.5µM 范围内。L-和 D-DOPA、组氨酸、多巴胺、血清素、（2-氨基乙基）吡啶/哌嗪和吗啉（K 值在 8.3µM-14.5µM 之间）也表现出适度的激活作用，而最佳的激活剂是 L-和 D-Trp、L-和 D-Tyr 和 4-氨基-Phe，其 K 值在 3.0µM-5.1µM 之间。详细了解β-CAs 的激活机制可能对设计具有潜在临床意义的酶活性调节剂具有重要意义。
